Effects of cross-linked high-molecular-weight hyaluronic acid on epidural fibrosis: experimental study

Abstract

<jats:sec> <jats:title>OBJECT</jats:title> <jats:p>Epidural fibrosis is nonphysiological scar formation, usually at the site of neurosurgical access into the spinal canal, in the intimate vicinity of and around the origin of the radicular sheath. The formation of dense fibrous tissue causes lumbar and radicular pain. In addition to radicular symptoms, the formation of scar tissue may cause problems during reoperation. The authors aimed to investigate the effects of cross-linked high-molecular-weight hyaluronic acid (HA), an HA derivative known as HA gel, on the prevention of epidural fibrosis by using histopathological and biochemical parameters.</jats:p></jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>Fifty-six adult female Sprague-Dawley rats were evaluated. The rats were divided into 4 groups. Rats in the sham group (n = 14) underwent laminectomy and discectomy and received no treatment; rats in the control group (n = 14) underwent laminectomy and discectomy and received 0.9% NaCl treatment in the surgical area; rats in the HA group (n = 14) received HA treatment at the surgical area after laminectomy and discectomy; and rats in the HA gel group (n = 14) underwent laminectomy and discectomy in addition to receiving treatment with cross-linked high-molecular-weight HA in the surgical area. All rats were decapitated after 4 weeks, and the specimens were evaluated histopathologically and biochemically. The results were statistically compared using the Mann-Whitney U-test.</jats:p></jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>Compared with the sham and control groups, the HA and HA gel groups showed significantly lower fibroblast cell density and tissue hydroxyproline concentrations (p &lt; 0.05). There was statistically significant lower dural adhesion and foreign-body reaction between the control and HA gel groups (p &lt; 0.05). Granulation tissue and epidural fibrosis were significantly lower in the HA and HA gel groups compared with the sham group (p &lt; 0.05). There were no significant differences in any histopathological parameters or biochemical values between Groups 3 and 4 (p &gt; 0.05).</jats:p></jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>Cross-linked high-molecular-weight HA had positive effects on the prevention of epidural fibrosis and the reduction of fibrotic tissue density. The efficacy of this agent should also be verified in further experimental and clinical studies.</jats:p></jats:sec>

Prospective application of stem cells to prevent post‐operative skeletal fibrosis

“…More evidence indicates that some biomaterials have been successfully used to prevent post-operative skeletal fibrosis in animal models, including hyaluronic acid (HA) and derivatives, [45][46][47][48][49][50] chitosan and derivatives [51][52][53] and amniotic membrane and derivatives. [54][55][56][57] Specifically, topical application of HA derivatives could prevent peritendinous fibrosis in patients.…”

A novel bacterial cellulose membrane immobilized with human umbilical cord mesenchymal stem cells-derived exosome prevents epidural fibrosis

“…To date, most biomaterials, such as Adcon-L gel, carboxymethylcellulose/ polyethylene oxide, polyethylene glycol hydrogel, hyaluronic acid, and poly L-glutamic acid/chitosan composite, have been applied in preventing epidural fibrosis. [4][5][6][7][8] However, pain, tachycardia, skin erythema, high cost, and suboptimal prevention of epidural fibrosis have restricted their further application in practice. 9,10 Therefore, it is urgent to explore a simple and convenient method to fabricate a tunable material in the prevention of epidural fibrosis.…”

The Role of Pharmacological Agents in Nerve Regeneration after Peripheral Nerve Repair

“…There are various commercial preparations of HA in different forms, such as films, microspheres, liposomes, fibres and hydrogels, which have been used for more than 20 years worldwide [63]. Although the abovementioned commercial preparations of HA have mainly been used in animal studies, it also provides useful information regarding the effect of hyaluronate in the prevention of postoperative peridural scar adhesion after laminectomy in spine surgery; however, additional clinical trials regarding the use of HA-based gels should be performed to confirm its effects in human subjects [67,68]. Use of the hyaluronic acid-carboxymethylcellulose membrane Seprafilm as a solid anti-adhesion barrier agent is one of the therapeutic approaches used to reduce postoperative scar formation and is effective in promoting peripheral nerve regeneration at the repair site [69].…”